Cancer Therapy Using Ion Accelerators · Thomas Haberer Heidelberg Ion Therapy Center Cern Accelerator School 2009 Cancer Therapy Using Ion Accelerators. Th. Haberer, Heidelberg Ion

Thomas HabererHeidelberg Ion Therapy CenterCern Accelerator School 2009

Cancer Therapy Using Ion Accelerators

Th. Haberer, Heidelberg Ion Therapy Center

Rationale / Physics

• inverted depth-dosedistribution

• mild lateral scattering

Increased Relative Biological Effectiveness

RBEs:

Plateau: ~1.4

Peak: ~ 2.3


radiation induced myelopathy in rats after 2 carbon fractions

Debus, Karger, Peschke, Scholz, …Rad. Res. 2003

GoalThe key element to improve the clinical

outcome is local control!

entrance channel:• low physical dose• low rel. biol. effiency

tumour:• high physical dose• high rel. biol. effiency


Standard Approach

• Facilities being built at existing researchaccelerators

• Fixed energy machineswith moderate flexibility(if at all)

• Dose delivery not exactlytumor-conform

Ernest Orlando Lawrence Nobel Prize 1939


184 inch Cyclotron @ LBL 1947 / 1986


Th. Haberer, Heidelberg Iontherapy Center

Passive Dose Delivery


Standard / System + Dose Distr.typical set-up(Tsukuba) Distal edge shaping using a bolus

pulls dose back into healthy tissue


Situation / Clinical Centers

• In 1994 the firstdedicated clinic-basedfacilities, LLMUC (protons) and HIMAC (carbon), started

• Nowadays more than50 proton treatmentprotocols areapproved and reimbursed in the US

• LLUMC treats up to 180 patients per day

Heavy Ion Medical Accelerator, Chiba, Japan



Dose Delivery Concept @ GSI/HITRealization:Dissect the treatment volumeinto thousands of voxels. Usesmall pencil beams with a spatial resolution of a few mm to fill each voxel with a pre-calculated amount of stoppingparticles taking into accountthe underlying physical and biological interactions.

⇒ Extreme intensitymodulation viarasterscanning

Idea:Dose distributions of utmosttumor conformity can beproduced by superimposingmany thousands Bragg-peaksin 3D. Sophisticated requirementsconcerning the beam delivery system, the accelerator, thetreatment planning, QA, ... result from this approach.


Beam Scanning

Ions (Haberer et al., GSI): raster scanning, 3D active,2D magnetic pencil beam scanningplusactive range stacking (spot size, intensity)in the accelerator

• Protons (Pedroni et al., PSI):spot scanning gantry1D magnetic pencil beamscanning

• plus passive range stacking(digital range shifter)


Active / Fluence Distribution

Fluence distribution of a single slice through thetarget volume

Accelerator requirements• scanning ready pencil beam library:

• energy: up to 30 cm WE, ~1 mm steps, ∆E/E ~1% p: 48 – 200 MeV, C: 88 – 430 MeV/u

• spot sizes: 4 – 10 mm (3-4 steps), 2D Gaussian• intensity: ~1010 (p), ~108 (C) per spill

• ~ 100.000 combinations• beam purity• several quasi parallel particle types

– change of particle type < 60 s• availability ~95%• low operational & maintenance cost

The Proton Data Base for HIT

K. Parodiand A. Mairani,(HIT and FLUKA Collaboration)

Rasterscan Method

scanning offocussedion beamsin fastdipole magnets

active variationof the energy,focus andintensity in theaccelerator andbeam lines

Haberer et al., NIM A , 1993

Proton-Synchrotron, Shizuoka, Japan

Cyclotron-based


Cyclotron-based


Economic requirements• change of particle type < 60 s (dead time)

• change of treatment room < 30 s (dead time)

• number of treatment rooms utilization of accelerator

• 300 days per year, 16 hours per day• ~1-2 min per treatment field (~1l, ~1-2 Gy)

(target fraction duration: 15 min incl. 4 min beam)

• initial cost• operational & maintenance cost

Scanned Carbon vs. Intensity Modulated Photons

scanned carbon 3 fields IMRT 9 fields

reduced integral dosesteeper dose gradientsless fieldsincreased biological effectiveness

courtesy O. Jäkel, HIT


Therapy @ GSI


Process

• patient immobilization• 3D-imaging (CT, MRI, PET, ...)• definition of target volume + organs at risk• definition of treatment modality• dose calculation + treatmentplan evaluation• patient positioning• treatment• follow-up


• couple a coord.-system to thebody

• localizer withfiducials

• calculatestereotacticcoordinates forthe target

Stereotactic Immobilization


Treatment Planning1960: contours

in 1 plane only

today: 3D dataset, densitycorrection, ...


Treatment Planning


Pencil Beam Position• position of the pencil beam depends on the beam energy

and the beam spot size• check the position and width at the iso-center using a

tungsten sphere in front of a X-ray film


QA / Rasterscansystem

homogeneityof 2d dose distributions


QA / Rasterscansystem

verification of depth-dosedistributions


Patient Positioning• alignment with the

room laser system• setting of the

stereotacticcoordinates


Position Verification

• comparison of X-rayimage with a digitallyreconstructed X-rayimage (source: planningCT)

• accuracy at the base of the scull 1-2 mm (Karger 2001, IJROBP)


Combined photon and carbon ion RT foradenoid cystic carcinomas

clinical phase I/II trial

Treatment parametersPhoton IMRT 54 Gy to the CTV

+

carbon ion boost 18 GyE (6x3.0 GyE) to the GTV


early toxicity acceptablelate toxicity > CTC grade 2 < 5%

FSRT / IMRT vs FSRT / IMRT+C12 :locally advanced adenoidcystic carzinoma

overall survival local control

Schulz-Ertner, Cancer 2005

Heidelberg University Hospital


• compact design• full clinical

integration• rasterscanning only• low-LET modality:

Protons (later He)• high-LET modality:

Carbon (Oxygen)• ion selection within

minutes• world-wide first

scanningion gantry

• > 1000 patients/year> 15.000 fractions/year

• integrated R+D-infrastructure

Heidelberg Ion Therapy Center

• Effective area 5.027 m²• Concrete 30.000 tons • Constructional steel 7.500 tons• Capital Investment 106 M€

Project Partners:• University pays, owns and

operates the facility• GSI built the accelerator• Siemens supplies all components

related to patient environmentGSI, DKFZ, Siemens …are research partners

Start of construction: November 2003Completion of building and acc.: June 2006Accelerator settings established: April 2008First patient planned: 2nd half of 2009

Germany: Ion Facility of the Heidelberg Some Facts

HIT Accelerator System

InjectorIon sources

SynchrotronHEBT+GantryMedical Areas


HIT / Linac

RFQ

Ion source

• compactdesign

• proven technology• fast change of the ion species

• fast intensityvariation(1000-times)

• constantbeam parameter

Cooperation: GSI + IAP@ Univ. Frankfurt/M.


HIT / Synchrotron

Multiturn injection

Multiple extraction

0,5 bis 10 sec

• compact design

• proven technology

• multiturn-injection => high intensities

• rasterscanningoptimized, extremelyflexible beamextraction

• fast variationof energy(range)

RF-KO-Extraction• Principle

– resonant HF-excitation (betatron frequency)– constant separatrix

• Characteristcs– slow extraction– constant ion-optical settings dring extraction– Multiple extractions available– Spillshaping via amplitude modulation

Th. Haberer

Synchroton/HEBT Commissioning

Daily ACC-QA, March 2009


Accelerator Status• Sources, injector and synchrotron fully commissioned for

protons, carbon and oxygen (256 energies each)• H1 / H2: pencil beam libraries ( E F I ) for protons and carbon in

therapeutical quality reached in April, 2008outstanding beam quality: very high position and focus stability,small intensity fluctuations

• R+D-cave: protons, carbon and oxygen energy libs established• Gantry: proof of principle for protons and carbon

(representative settings in the full phase space ( E F I α ))• To do: intensity upgrade ( x3 ) under way (sources, LEBT, RFQ)• Operation scheme:

2007: 24 h / 5 days 2008ff: 24 h / 7 days, 330 days, 2 shutdowns 14 days each

• Availability of the pencil beams @ H1/2: ≈ 98%

Advantages of a synchrotron

• It works and fulfills all requirements.

• proven technology• stable & reliable operation• built-in flexibility

(particle types, energy, timing)• active energy variation

– maximum beam purity– minimum radiation protection effort

Disadvantages of a synchrotron

Particle therapy facility• size of foot print• initial cost• (several treatment rooms required)

Objections (no real disadvantages)• current uniformity• repetition rate

HIT GSI

• 440 patients• each field verified

ACC Conclusion

• gold standard in ion therapy: SYNCHROTRON– all C-patients: NIRS, GSI– new facilities: HIT, CNAO, Marburg, NROCK, Gunma

• future– improved accelerators wellcome

• lower initial, operational, maintenance cost

– HOWEVER• decrease in treatment quality unacceptable• loss of flexibility questionable (25 years)


Dose Delivery and Medical EquipmentIdentical patientpositioning systems • fixed beam• Gantry

Workflow optimization• automated QA

procedures• automated patient

hand over from shuttle

Inroom positionverification• 2D• 3D Cone beam CT

Open for futureapplications andworkflows

Commissioning

commissioning result, Protons @ H1:3d dose delivery vs. treatment planning24 thimble-type ICs in a water phantom, standard deviation 2.2 % QA Table Top with Water Phantom

Th. Haberer

Motivation Gantry

Advantage of a rotating

beamline

Pancreas, supine position via gantry advantageous


ACCEL / SEAG

• optimum doseapplication

• world-wide firstion gantry

• world-wide firstintegrationof beam scanning

• 13m diameter25m length600to overall weight0,5mm max. deformation

• prototype segmenttested at GSI

Scanning Ion Gantry

MT Mechatronics

The HIT Gantry Rotates

Gantry: first beam

at theisocenter

January 4th, 2008

Thank you for your attention !

(Intensity modulated raster scan, 12C at 430 Mev/u, October 15th 2007)

Documents

Cancer Therapy Using Ion Accelerators · Thomas Haberer Heidelberg Ion Therapy Center Cern Accelerator School 2009 Cancer Therapy Using Ion Accelerators. Th. Haberer, Heidelberg Ion